Overview
Availability
- Associate Professor Mark Smythe is:
- Available for supervision
- Media expert
Fields of research
Qualifications
- Bachelor of Science, James Cook University
- Bachelor (Honours) of Science (Advanced), James Cook University
- Doctor of Philosophy, University of Melbourne
Research interests
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Combinatorial Chemistry and Molecular Design
The approach is to combine protein structural information with combinatorial chemistry, resulting in the design and synthesis of molecules that mimic protein structure, ultimately leading to the discovery of compounds that mimic protein function. We are actively pursuing small molecules for cytokine and G-protein coupled receptors.
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Protein-protein interactions
Many biological processes are carried out, or regulated, through protein-protein interactions. Despite their physiological significance, they remain one of the most difficult molecular recognition events to inhibit or mimic. We have developed molecular design processes that successfully identify small molecular candidates which modulate the function of protein-protein interactions. We currently have several lead molecules against numerous protein-protein interaction targets.
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Molecular design
We have developed an integrated design platform for library design and structure-based design of molecules that modulate protein-protein interactions. This approach includes a set of unique biological descriptors for library design, a purpose-built virtual screening of virtual library platform and databases comprising large virtual libraries of compounds. Using these methodologies we design and synthesise arrays of molecules that sample biologically relevant diversity space for primary screening, as well as arrays of molecules specifically targetted for a therapeutic protein of interest.
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Combinatorial chemistry
Current strategies in library design involve the calculation of hundreds of potential descriptors that define various chemical characteristics, and selecting a diverse set of compounds in this descriptor space. With hundreds of available descriptors it is difficult to know which descriptors, if any, are important or essential for describing biological activity. Consequently such procedures result in the optimisation of libraries in chemical descriptor space, which has little impact on biologically relevant regions of that space. To overcome this we have developed a series of biologically-relevant descriptors that are used in library design. As a consequence, we aim to identify the biologically-relevant structural regions of chemical diversity and design and synthesise arrays of molecules that match this diversity space. We have developed new linkers and auxiliaries to aid combinatorial synthesis and a molecular design platform to achieve these objectives. We have synthesised various constrained cyclic peptide libraries (molecular toolkit libraries) and libraries of macrocycles and heterocycles. We have a particular focus on the discovery and exploitation of privileged structures.
Works
Search Professor Mark Smythe’s works on UQ eSpace
1994
Journal Article
DESIGN AND SYNTHESIS OF A BIOLOGICALLY-ACTIVE ANTIBODY MIMIC BASED ON AN ANTIBODY-ANTIGEN CRYSTAL-STRUCTURE
SMYTHE, ML and VONITZSTEIN, M (1994). DESIGN AND SYNTHESIS OF A BIOLOGICALLY-ACTIVE ANTIBODY MIMIC BASED ON AN ANTIBODY-ANTIGEN CRYSTAL-STRUCTURE. Journal of the American Chemical Society, 116 (7), 2725-2733. doi: 10.1021/ja00086a005
1993
Journal Article
FREE-ENERGY PROFILE OF A 3(10)-HELICAL TO ALPHA-HELICAL TRANSITION OF AN OLIGOPEPTIDE IN VARIOUS SOLVENTS
SMYTHE, ML, HUSTON, SE and MARSHALL, GR (1993). FREE-ENERGY PROFILE OF A 3(10)-HELICAL TO ALPHA-HELICAL TRANSITION OF AN OLIGOPEPTIDE IN VARIOUS SOLVENTS. Journal of the American Chemical Society, 115 (24), 11594-11595. doi: 10.1021/ja00077a067
1993
Journal Article
RATIONAL DESIGN OF POTENT SIALIDASE-BASED INHIBITORS OF INFLUENZA-VIRUS REPLICATION
VONITZSTEIN, M, WU, WY, KOK, GB, PEGG, MS, DYASON, JC, JIN, B, PHAN, TV, SMYTHE, ML, WHITE, HF, OLIVER, SW, COLMAN, PM, VARGHESE, JN, RYAN, DM, WOODS, JM, BETHELL, RC, HOTHAM, VJ, CAMERON, JM and PENN, CR (1993). RATIONAL DESIGN OF POTENT SIALIDASE-BASED INHIBITORS OF INFLUENZA-VIRUS REPLICATION. Nature, 363 (6428), 418-423. doi: 10.1038/363418a0
Funding
Current funding
Past funding
Supervision
Availability
- Associate Professor Mark Smythe is:
- Available for supervision
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Supervision history
Current supervision
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Doctor Philosophy
Towards the Treatment of Duchenne Muscular Dystrophy
Principal Advisor
Other advisors: Associate Professor Peter Noakes
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Doctor Philosophy
Assessing the therapeutic effects of our novel compound `PK007¿ in DMD model mice by inhibiting pro-inflammatory prostaglandin D2 synthesis.
Principal Advisor
Other advisors: Associate Professor Peter Noakes
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Doctor Philosophy
Blocking the sensing function of activated glia during neuroinflammation
Principal Advisor
Other advisors: Associate Professor Peter Noakes
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Doctor Philosophy
Blocking the sensing function of activated glia during neuroinflammation
Principal Advisor
Other advisors: Associate Professor Peter Noakes
Completed supervision
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2008
Doctor Philosophy
Drugs for undruggable targets and other impossibilities: The development of molecular scaffolds for more efficient drug design and development
Principal Advisor
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2005
Doctor Philosophy
THE SYNTHESIS OF PRIVILEGED SUBSTRUCTURES
Principal Advisor
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2007
Doctor Philosophy
THE STRUCTURAL BASIS FOR INTERACTION BETWEEN COLONY- STIMULATING FACTOR-1 AND ITS RECEPTOR, CSF-1R
Associate Advisor
Other advisors: Professor David Hume, Professor Bostjan Kobe, Dr Ian Ross
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2004
Doctor Philosophy
COMBINATORIAL METHODS AND APPLICATIONS IN DRUG DISCOVERY
Associate Advisor
Media
Enquiries
Contact Associate Professor Mark Smythe directly for media enquiries about:
- asthma
- Chemistry - combinatorial
- Chemistry - computational
- Computational chemistry
- Drug design
- drug development
- drug discovery
- inflammatory bowel disease
- leukaemia
- Molecular modelling
- peptides
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